Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity.

Leptin is a peptide hormone that regulates fat stores in the body and appetite by controlling the feeling of satiety. This hormone is secreted by the white adipose tissue and plays a role in the storage and mobilization of fatty acids. Mutations of the LEP gene have been associated with obesity in d...

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Publicado en:BioMed Research International pp. 1 - 11
Autores principales: Bouafi, Hind, Bencheikh, Sara, Mehdi Krami, A. L., Morjane, Imane, Charoute, Hicham, Rouba, Hassan, Saile, Rachid, Benhnini, Fouad, Barakat, Abdelhamid
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 12/4/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 12/4/2019
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2019/1832084
        140076114
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        atl: Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity.
      aug:
        au:
          Bouafi, Hind
          Bencheikh, Sara
          Mehdi Krami, A. L.
          Morjane, Imane
          Charoute, Hicham
          Rouba, Hassan
          Saile, Rachid
          Benhnini, Fouad
          Barakat, Abdelhamid
        affil: Laboratoire de Génomique et Génétique Humaine, Institut Pasteur du Maroc, Casablanca, Morocco
      sug:
        subj:
          Disease Susceptibility
          Polymorphism, Genetic
          Leptin
          Obesity Familial and Genetic
          Human
          Fatty Acids
          Mutation
          Bioinformatics
          Amino Acids
          Proteins
      ab: Leptin is a peptide hormone that regulates fat stores in the body and appetite by controlling the feeling of satiety. This hormone is secreted by the white adipose tissue and plays a role in the storage and mobilization of fatty acids. Mutations of the LEP gene have been associated with obesity in different populations; it is a multifactorial disease that constitutes a major public health problem. In this study, we evaluated the impact of missense SNPs in the LEP gene extracted from dbSNP using 8 computational prediction tools. Out of the total of 4337 SNPs, 93 were nsSNPs (nonsynonymous single nucleotide polymorphisms). Among 93 nsSNPs, 12 (S46L, G59S, D61N, D100N, N103K, C117S, D76V, S88C, P90R, I95N, L161R, and R105W) variants were predicted to be the most deleterious by prediction software. On these 12 deleterious SNPs, 8 variants (S46L, G59S, D61N, D100N, N103K, C117S, L161R, and R105W) were located in the conserved positions and showed a decrease in structure stability which was evaluated by I-Mutant and Mupro. Then, by analyzing the different interactions between different amino acids in wild and mutated proteins, we assessed the structural impact of the deleterious modifications using the YASARA software. Among 8 deleterious nsSNPs, we revealed structure changes in the 6 variants S46L, G59S, D100N, L103K, R105W, L161R, two of which R105W, N103K were previously reported as associated with obesity. Our study suggests 6 deleterious mutations could play an important role in contributing to human obesity and worth to be included in association and functional studies, then may be a drug target.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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